EP2862595A1 - Omnidirektionales, entfaltbares, neuronales Mehrkanal-Elektrodensystem - Google Patents

Omnidirektionales, entfaltbares, neuronales Mehrkanal-Elektrodensystem Download PDF

Info

Publication number
EP2862595A1
EP2862595A1 EP20140189810 EP14189810A EP2862595A1 EP 2862595 A1 EP2862595 A1 EP 2862595A1 EP 20140189810 EP20140189810 EP 20140189810 EP 14189810 A EP14189810 A EP 14189810A EP 2862595 A1 EP2862595 A1 EP 2862595A1
Authority
EP
European Patent Office
Prior art keywords
carrier
proximal
distal
channel
neural
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP20140189810
Other languages
English (en)
French (fr)
Other versions
EP2862595B1 (de
Inventor
David S. Pellinen
Bencharong Suwarato
Rio J. Vetter
Jamille Farraye Hetke
Daryl R. Kipke
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
NeuroNexus Technologies Inc
Original Assignee
NeuroNexus Technologies Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by NeuroNexus Technologies Inc filed Critical NeuroNexus Technologies Inc
Priority to EP17175025.0A priority Critical patent/EP3254726B1/de
Publication of EP2862595A1 publication Critical patent/EP2862595A1/de
Application granted granted Critical
Publication of EP2862595B1 publication Critical patent/EP2862595B1/de
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0551—Spinal or peripheral nerve electrodes
    • A61N1/0558—Anchoring or fixation means therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
    • A61B5/293—Invasive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0021—Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023—Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026—Multi-lumen catheters with stationary elements
    • A61M25/003—Multi-lumen catheters with stationary elements characterized by features relating to least one lumen located at the distal part of the catheter, e.g. filters, plugs or valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0068—Static characteristics of the catheter tip, e.g. shape, atraumatic tip, curved tip or tip structure
    • A61M25/007—Side holes, e.g. their profiles or arrangements; Provisions to keep side holes unblocked
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0529—Electrodes for brain stimulation
    • A61N1/0534—Electrodes for deep brain stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/36017—External stimulators, e.g. with patch electrodes with leads or electrodes penetrating the skin
    • G—PHYSICS
    • G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
    • G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
    • G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
    • G03F7/26—Processing photosensitive materials; Apparatus therefor
    • G03F7/40—Treatment after imagewise removal, e.g. baking
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0021—Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023—Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026—Multi-lumen catheters with stationary elements
    • A61M25/003—Multi-lumen catheters with stationary elements characterized by features relating to least one lumen located at the distal part of the catheter, e.g. filters, plugs or valves
    • A61M2025/0031—Multi-lumen catheters with stationary elements characterized by features relating to least one lumen located at the distal part of the catheter, e.g. filters, plugs or valves characterized by lumina for withdrawing or delivering, i.e. used for extracorporeal circuit treatment

Definitions

  • the invention relates to the field of devices and methods used for neural interventions. More particularly, the present invention relates to a neural probe comprising an electrode array of at least one of a stimulation electrode and a recording electrode.
  • the electrode array is supported on a carrier having a shape and structure similar to a carpenter's tape spring.
  • the tape spring-type carrier provides the electrode array with stiffness along a line of trajectory once deployed into body tissue, but with a degree of flexibility that allows the electrode array to move with the tissue.
  • DBS Deep Brain Stimulation
  • Conventional DBS therapy involves controllable electrical stimulation through a lead having four relatively large electrodes that are implanted in the targeted region of the brain. While conventional DBS therapy is generally safe and effective for reducing cardinal symptoms of the approved diseases, it often has significant behavioral and cognitive side effects and limits on performance. Additionally, the therapeutic effect is highly a function of electrode position with respect to the targeted volume of tissue, and more specifically, a function of which neuronal structures are influenced by the charge being delivered. With conventional electrodes, there are limitations as to how the charge is delivered and stimulation fields are limited as all of the electrode sites involved with stimulation are positioned along a single axis.
  • the neural intervention system 10 comprises a guide tube 12 supporting a plurality of deployment channels 14 that are configured to direct the delivery of a number of neural probes 16 into body tissue 18.
  • neural intervention system 10 is designed for use in deep brain stimulation procedures and more specifically, for interface with deep brain tissue in a three-dimensional manner.
  • the neural intervention system 10 may alternatively be used in any suitable environment such as with the spinal cord, peripheral nerves, muscles, or any other suitable anatomical location.
  • the chamber 20 is where the ribbon cables 19 connect to an electronic subsystem (not shown) that serves as an interface to any one of a number of external devices, such as implantable pulse generator (IPG) 17.
  • IPG implantable pulse generator
  • Other electrical subsystems include, but are not limited to, a printed circuit board with or without on-board integrated circuits and/or on-chip circuitry for signal conditioning and/or stimulus generation, an Application Specific Integrated Circuit (ASIC), a multiplexer chip, a buffer amplifier, an electronics interface, an implantable rechargeable battery, integrated electronics for either real-time signal processing of the input (recorded) or output (stimulation) signals, integrated electronics for control of the fluidic components, any other suitable electrical subsystem, or any combination thereof.
  • the skull chamber 20 is not needed and the ribbon cables 19 connect directly to any one of the above listed external devices.
  • the guide tube 12 is preferably made of a rigid material that can be inserted into tissue or other substances without buckling and can maintain a generally straight trajectory through the tissue 18.
  • the material may be uniformly rigid, or rigid only in a particular direction (such as the axial direction).
  • the guide tube material is preferably plastic (such as a medical grade plastic) or metallic (such as titanium), but may alternatively be any suitable material such as metal or a combination of materials.
  • the distal tube portion 12B includes a rounded or curved tip 12D designed to prevent undue trauma to body tissue as the guide tube is inserted therein.
  • FIG. 3A illustrates an alternate embodiment of a sharpened tip 12D' adapted to penetrate tissue and aid in insertion of the guide tube therein.
  • the guide tube 12 is maneuverable into the tissue in a three-dimensional arrangement.
  • a maneuverable guide tube 12 may include a system of cables, joints, connections, or robotics that is controlled by a user to position the guide tube in a desired position in the tissue.
  • the maneuverable guide tube 12 may also be guidable remotely and/or wirelessly.
  • the distal portion 12B of the guide tube includes at least one, and preferably a plurality of deployment channels.
  • Exemplary deployment channel 14 ( FIG. 4 ) comprises a proximal channel portion 14A spaced from a distal channel portion 14B.
  • the exemplary deployment channel 14 has a lumen 22 extending from a proximal open end 22A adjacent to the proximal channel portion 14A to a distal open end 22B adjacent to the distal channel portion 14B.
  • the proximal and distal open ends 22A, 22B are not aligned along a common axis.
  • lumen 22 extends from a proximal open end 22A residing along a plane B-B aligned substantially perpendicular to the longitudinal axis A-A of the guide tube 12 to a distal open end 22B serving as an open port at the guide tube sidewall 12A.
  • a proximal open end 22A residing along a plane B-B aligned substantially perpendicular to the longitudinal axis A-A of the guide tube 12 to a distal open end 22B serving as an open port at the guide tube sidewall 12A.
  • the path from the proximal open end 22A to the distal open end 22B is substantially a right angle.
  • FIG. 3B illustrates an embodiment where the lumen 22 from proximal open end 22A to distal open end 22B of channel 14 is bisected by an imaginary plane C-C aligned along axis A-A.
  • FIG. 3C illustrates the lumen path 24 of a second exemplary one of the deployment channels 26 deviating from a proximal open end 26A bisected by plane D-D aligned along axis A-A to a distal open end 26B angularly deviating from plane D-D.
  • the angular deviation can be in either the clockwise or counter-clockwise directions.
  • a third exemplary one of the deployment channels 32 has its proximal open end 32A residing along the imaginary plane B-B aligned perpendicular to axis A-A and with its distal open end 32B exiting the guide tube sidewall 12A so that the lumen follows a path forming a substantially obtuse angle with respect to axis A-A.
  • a fourth exemplary one of the deployment channels 34 has its proximal open end 34A residing along the imaginary plane B-B, but with its distal open end 34B exiting the guide tube sidewall 12A so that the lumen follows a path forming a substantially acute angle with respect to axis A-A.
  • a deployment channel can provide a lumen that follows a path incorporating a combination of those described with respect to the first to the fourth exemplary channels 14, 26, 32 and 34.
  • the trajectory of the distal channel portion defining the distal open end 22B, 32B and 34B ranges from about 10° to 180° with respect to axis A-A.
  • distal open end 32B is more proximal than distal open end 34B. That is even though their respective proximal open ends 32A, 34A reside along plane B-B.
  • the exemplary deployment channels 14, 26, 32 and 34 can be angled in many different orientations. That is for the purpose of introducing a plurality of neural probes 16 into a target body tissue at any one of a number of trajectories off axis from axis A-A of the guide tube 12. This greatly improves the footprint of deployed electrodes so that multiple spatially separate stimulation and recording channels radiate outwardly from the distal portion 12B of the guide tube.
  • Enhanced deployment of neural probes 16 makes it possible to spontaneously record neuronal activity, movement-related activity, or evoked activity as a result of stimulation from nearby sites. Simultaneously sampled recordings could be exploited to increase the speed and accuracy by which data are acquired. With respect to stimulation, this three-dimensional arrangement of neural probes 16 can be used in either monopolar or bipolar modes to steer current to desired body tissue locations.
  • FIG. 2A is an enlarged view of the distal end 12D of the guide tube.
  • This view shows that the distal open ends 22B of exemplary deployment channel 14 can reside on the distal guide tube end 12D. That is in addition to or instead of the distal open end of a channel residing on the cylindrical sidewall 12A as shown in FIG. 2 . While it is preferred that the distal open end of a deployment channel have an elongate shape with opposed curved sidewalls, that is not necessary.
  • Open end 22C has a rectangular shape without curved sidewalls.
  • FIGs. 4, 4A, 4B , 5 , 5A and 5B illustrate a novel aspect of a neural probe 16 according to the present invention.
  • the neural probe 16 comprises opposed first and second electrodes 36 and 38 comprising an electrode array supported by a tape-spring-type carrier 40.
  • the carrier 40 is of a metal, preferably selected from tungsten, stainless steel, platinum-iridium, or of a polymeric material, and in an unstressed condition has a shape similar to a carpenter's tape for a tape measure.
  • the tape spring-type carrier 40 flexes to permit the neural probe 16 to readily bend, thereby when in a stressed condition collapsing into a shape having a linear cross-section 40A ( FIG.
  • That portion of the tape spring-type carrier 40 residing in the proximal portion 14A of the deployment channel 14 adjacent to the proximal open end 22A has the concave tape spring-type shape 40B ( FIG. 4AB ).
  • that portion of the carrier 40 residing in the distal portion 14B of the deployment channel adjacent to the distal open end 22B and extending out therefrom has reassumed the tape spring shape.
  • the tape spring-type shape of the carrier 40 provides the neural probe 16 with a degree of linear rigidity along the trajectory of the distal channel portion 14B and outwardly therefrom that is not available with prior art probes.
  • FIG. 4B shows that the curved cross-sectional shape of the tape spring-type carrier 40 can be concave having a focal point 42 residing outside plane E-E extending through the carrier's opposed ends.
  • the curve cross-sectional shape of the tape spring-type carrier can also be that of a parabola.
  • FIGs. 5 , 5A and 5B show the tape spring-type carrier 40 sandwiched between opposed polymeric layers 40A and 40B. If the carrier 40 is of a polymeric material, then layers 40A and 40 are of a different polymeric material. Electrode 36 is exemplary of a stimulation electrode while electrode 38 is exemplary of a recoding electrode. The stimulation electrode 36 is configured for electrical stimulation of biological tissue and recording electrode 38 is configured for recording of biological activity from biological tissue. The stimulation electrode 36 is sandwiched between opposed dielectric layers 37A and 37B. Likewise, recording electrode 38 is sandwiched between opposed dielectric layers 39A and 39B. The electrode sites 36, 38 are preferably metal such as iridium, platinum, gold, but may alternatively be any other suitable material. Polyimide, parylene, inorganic dielectrics such as silicon carbide or aluminum oxide, or a composite stack of silicon dioxide and silicon nitride is preferably used for the dielectric layers 39A, 39B.
  • interconnects 36A, 38A depict electrical interconnects running the length of the neural probe.
  • interconnects 36A, 38A are of a lesser cross-section than the respective electrodes 36, 38.
  • the conductive interconnects 36A, 38A are preferably metal or polysilicon, but may alternatively be any other suitable material.
  • Interconnects 36A and 38A preferably terminate with electrical contacts or bond pads (not shown) at their proximal ends. That is for electrical connection of the electrodes 36, 38 to external instrumentation and/or hybrid chips, such as depicted by IPG 17 in FIG. 1 .
  • suitable configurations for electrodes and interconnects for use with neural probes 16 reference is made to U.S. Patent No. 7,941,202 to Hetke et al. , which is assigned to the assignee of the present invention and incorporated herein by reference.
  • FIG. 5A shows the entire electrode structure having a curved shape mimicking that of the tape spring-type carrier. This is contrast to the electrode structure shown in FIG. 5 having generally planar electrode faces.
  • FIG. 5B shows an electrode supported on only one side of the tape spring-type carrier 40.
  • the electrode array preferably includes sixty-four stimulation electrodes 36 and thirty-two recording electrodes 38 positioned around and along the tape spring-type carrier 40.
  • Stimulation sites are also preferably spaced at 750 ⁇ m in the axial direction (center-to-center) and positioned at sixteen successive locations.
  • each row of stimulation electrode sites 36 two recording electrode sites 38 are preferably positioned on opposite sides of the tape spring-type carrier 40.
  • the position of each recording electrode site pair 38 preferably shifts ninety degrees between successive depths.
  • FIG. 2B is an enlarged view of representative deployment opening 22C showing opposed major sidewalls 23A and 23B and opposed minor sidewalls 23C and 23D.
  • Axis 22C' is centered therein and represents the trajectory a neural probe 16 comprising the tape spring-type carrier 40 of the present invention would take after having been deployed out from the opening 22C.
  • Representative trajectories 22B', 22C' and 22D' are also shown in FIG. 2 .
  • the neural probes 16 are connected to a manifold 44.
  • IPG implantable pulse generator
  • the probes 16 comprising the tape spring-type carrier 40 extend distally from the manifold 44 and are spaced at even or uneven intervals from each other.
  • the guide tube 12 can support more than one manifold/neural probe assembly. Two such assemblies 46, 48 are illustrated, but that is by way of example.
  • the neural intervention system 10 is constructed with the probes pre-registered with their respective channels. As previously discussed, FIG.
  • FIG. 3A which is similar to FIG. 2 , illustrates that the proximal open ends of the plurality of deployment channels are located along common plane B-B, substantially perpendicular to axis A-A.
  • the respective proximal open channel ends are arranged in concentric circles, the outer circle 50 corresponding to the first manifold/neural probe assembly 44 and the inner circle 52 corresponding to the second manifold/neural probe assembly 46.
  • the respective distal ends of the probes 16 are received in the proximal open ends of the channels 14.
  • FIG. 2 further shows an actuation mechanism for deploying the plurality of neural probes 16.
  • the actuation mechanism includes a plunger 48 connected to the first and second manifold/neural probe assembly 44, 48.
  • the distal face of plunger 48 has grooves (not shown) that are sized and configured to receive the upper edges of the respective manifolds 44 therein.
  • the opposite face of the plunger 48 supports a push rod 50.
  • the push rod extends to the proximal end 12C of the guide tube and has a length that is sufficient for a user to grasp and manipulate to move the plurality of probes 16 through their respective deployment channels and out the open ends thereof.
  • the neural probes 16 are of a sufficient length that with the plunger 48 moved distally along the tube 12 until the manifolds 44 are adjacent to the proximal open ends of the deployment channels, the probes extend through the exemplary deployment channels 14, 26, 32 and 34 and out the distal open ends thereof to penetrate tissue at distances sufficient to provide effective stimulation or recording capability. While two manifold/neural probe assemblies are shown in FIG. 2 , it is within the scope of the present invention that three or more such assemblies can be fitted into a single guide tube 12.
  • FIGs. 1A and 1B illustrate the guide tube 12 inserted into tissue 18 with a plurality of neural probes 16 deployed in a three-dimensional arrangement into the tissue.
  • the tape spring-type carrier 40 of the present invention shuttles the neural probes 16 into tissue or other substances in a straight-line or radial direction once the probe has exited the distal open end of its deployment channel.
  • the carrier 40 may include a sharpened end 16A adapted to penetrate tissue and aid in insertion of the neural probe 16 including the carrier 40 into tissue at trajectories off axis from that of the penetrating guide tube 12.
  • the carrier 40 is not a rigid structure.
  • the carrier has sufficient stiffness to follow a desired trajectory dictated by the trajectory axis of one of previously described exemplary opens 22C, 22D and 22E, but that will move in response to movement of the tissue into which the probe 16 has been deployed. That helps to prevent undue trauma to the body tissue while maintaining a desired degree of stimulation and recording efficacy.
  • FIG. 6 illustrates another embodiment of a neural intervention system 10A according to the present invention.
  • System 10A is similar to that shown in FIG. 2 except that the actuation mechanism for deploying the plurality of neural probes 16 does not include a manifold. Instead, the neural probes 16 are individually directly connected to the plunger 48 connected to the push rod 50.
  • IPG implantable pulse generator
  • FIG. 7 illustrates another embodiment of a neural intervention system 10B according to the present invention.
  • System 10B is similar to the system 10 shown in FIG. 1 except that the guide tube 12 has a branched portion 12E extending from the proximal guide tube end 12C.
  • the branched tube portion 12E houses the ribbon cables (not shown, but similar to those designated as 19 in FIG. 1A ) connected to IPG 17 as an exemplary electronic subsystem.
  • IPG 17 an exemplary electronic subsystem.
  • Port 52 provides an exit for push rod 50 of the actuation mechanism for deploying the plurality of neural probes 16 into tissue 18.
  • FIG. 8 illustrates a further embodiment of a neural intervention system 10C.
  • guide tube 12 can support a first, and preferably a plurality of first deployment channels 54 at a more distal location than a second, and preferably a plurality of second deployment channels 56.
  • the first deployment channels 54 have their proximal ends 54A supported by plate 58 connected to an inner surface of the guide tube sidewall 12A.
  • the distal open ends 54B provide a port in the guide tube sidewall 12A adjacent to the distal tube portion 12D.
  • the proximal ends 56A of the second deployment channels 56 are likewise supported by a second plate 60 connected to the inner guide tube sidewall.
  • Their distal open ends 56B provide a port in the guide tube sidewall 12A adjacent to the proximal tube end 12C.
  • a first push rod 62 serving as an actuation mechanism extends through an opening 60A in the second plate 60 and is connected to the proximal ends of neural probes 16 in registry with the first deployment channels 54.
  • a second push rod 64 serves as an actuation mechanism for deploying neural probes 16 in registry with the second deployment channels 56. It is noted that the proximal ends of first deployment channels 54 are radially closer to the longitudinal axis A-A than the proximal ends of the second deployment channels 56. That is to provide clearance so that the first push rod 62 does not interfere with the second push rod 64.
  • first and second sets of deployment channels 54, 56 are shown, it is within the scope of the present invention that there can be two, three or more deployment channels delineated from each other not by where their respective distal open ends exit the guide tube sidewall 12A, but where their proximal open ends reside inside the guide tube with respect to each other.
  • FIGs. 9 and 10 illustrate one method of making a neural probe according to the present invention.
  • a metal or composite tape spring 40 is provided in a roll.
  • the tape spring material is rolled out and fabricated to a desired shape.
  • the electrode structures 36 and 38 shown in FIGs. 5 , 5A and 5B are then affixed, such as with a suitable medical grade adhesive, to one or both sided of the tape spring-type carrier 40.
  • FIGs. 11 to 17 illustrate the steps for forming a neural probe 16 incorporating a tape spring-type carrier 40 according to a second embodiment of the present invention.
  • FIG. 11 shows a photo-resist material 102 is deposited on a manufacturing substrate 104.
  • the photo-resist 102 is patterned in a shape similar to that desired for the product tape spring-type carrier 40.
  • the substrate 104 is preferably made of glass or silicon, but may alternatively be made from any other suitable material.
  • the substrate 104 may be flexible, rigid, or semi rigid depending on the microfabrication tooling (organic electronics equipment can increasingly use flexible substrates such as in roll-to-roll manufacturing, whereas IC and MEMS microfabrication equipment use a rigid silicon substrate).
  • the substrate 104 has a thickness ranging from about 200 microns to about 925 microns, preferably greater than 500 microns.
  • the photo-resist material 102 is preferably a thin film of gel, photoresist, or other transparent or semi-transparent organic medium that can be patterned onto the substrate 104.
  • the photo-resist film 102 is preferably at least semi-transparent to allow passage of light from a UV light source through the photoresist material.
  • a UV light source For positive photoresists, the area that is exposed to the UV light can be developed away in a developer.
  • polymer at the area that is exposed to the UV light forms strong chemical bonds that can withstand a developer, while the unexposed area can be developed away in a developer.
  • the photo-resist film 102 can be deposited, patterned, exposed to UV light, and developed in any suitable thin film technique.
  • FIG. 12 illustrates that the photoresist 102 is subjected to heat so that it flows and forms a curved or parabolic upper surface 102A to the substrate 104 of a shape approximating the final tape spring-type carrier shape. Then, the heated photoresist is subjected to a Deep Reactive Ion Etching (DRIE) 106 process to duplicate the photoresist pattern 102A on the substrate upper surface 104A. After the DRIE process, the resulting structure will be cleaned by oxygen plasma or standard organic and inorganic wet cleaning process.
  • DRIE Deep Reactive Ion Etching
  • FIG. 13 shows that after cleaning, a metal or polymeric carrier layer 110 is deposited on the upper or outer surface 104A of the substrate.
  • the carrier layer 110 can be deposited using any suitable thin film, semiconductor, microelectromechanical systems (MEMS) manufacturing technique or other microfabrication process, such as physical vapor deposition. Exemplary techniques and processes include evaporation and sputtering deposition.
  • the carrier layer 110 preferably includes thermal conductive or electrical conductive material such as of platinum (Pt) or platinum-iridium, iridium oxide, titanium nitride, or any other metal, metal oxide, shape memory alloy, or conductive polymer having suitable electrically conductive properties.
  • the carrier layer 110 can also be of a polymeric material, such as of polyimide, but may alternatively be made from any other suitable material. Moreover, the carrier layer 110 can be of a resorbable material, which is resorbed into tissue after a period of time. With the carrier supporting an electrode array, upon resorption, the electrode array is left to float freely in the brain or other suitable tissue or material.
  • the bioresorbable polymer is preferably polyglycolide or polylactide, but may alternatively be made from any suitable bioresorbable material.
  • the carrier layer 110 is shown as a continuous layer and can be patterned ( FIG. 14 ) using any suitable wet etch or dry etch technique.
  • the mask (not shown) is a photodefined resist or any other masking material patterned directly or indirectly using standard photolithography techniques. After the carrier layer 110 is patterned, excess metal or polymeric layer is etched away, leaving the pattern of the tape spring behind. A lift-off process, as is well known to those skilled in the art, can also be used to leave the tape spring pattern.
  • FIG. 15 illustrates that polydimethylsilisane (PDMS) as an exemplary transfer material 112 is spun onto the carrier patterns 110 followed by mounting a second manufacturing substrate 114 thereon.
  • PDMS polydimethylsilisane
  • Polyimide can be used at this step instead of PDMS.
  • electrodes can be fabricated on the polyimide film before undergoing the layer transfer onto a new carrier.
  • the original manufacturing substrate 104/108 is removed exposing curved inner surfaces 110A of the patterned tape spring-shaped material. This can be achieved by wet or dry etching technique.
  • FIG. 16 shows that the second manufacturing substrate 114 is flipped upside down, and a polyimide material 116 is spun coated onto the exposed curved inner surfaces 110A.
  • FIG. 17 illustrates that a photolithography process is used to define the shape of the thusly fabricated tape spring-type carrier 40 with polyimide layers 40A and 40B coated on both sides. The result is the tape spring-type carrier 40 sandwiched between polymeric layers 40A, 40B shown in FIG. 5 , 5A and 5B .
  • FIGs. 18, 18A and 18B illustrate the steps for forming a neural probe 16 incorporating a tape spring-type carrier 40 according to a third embodiment of the present invention.
  • FIG. 18 shows a sheet of metal 200 including patterned carrier 40 and registration patterns 202.
  • the registration patterns 202 provide for registering the carrier sheet 200 to the electrode manufacturing substrate as shown in FIG. 5 , 5A and 5B .
  • Subsequent photolithographic processes will embed the carriers40 between polymer electrodes.
  • Microstamping is one exemplary process using a laser to engrave the sheet 200 with a patterned shape of the tape spring-type carrier.
  • Thermoplastic nanoimprint lithography is another suitable process.
  • Thermoplastic nanoimprint lithography uses a thin layer of imprint resist thermoplastic polymer spun-coated onto a substrate (not shown). Then the substrate, which has topological patterns of the tape spring shape, is brought into contact with the polymeric sheet 200 and the mold and sheet are pressed together under pressure. When heated up above the glass transition temperature of the polymer sheet 200, the pattern on the mold is pressed into the softened polymer. After cooling, the mold is separated from the sheet 200 and the tape spring pattern resist is left on the sheet 200.
  • a pattern transfer process reactive ion etching, normally
  • cold welding between two metal surfaces can be used to transfer low-dimensional nanostructured metal without heating (especially for critical sizes less than ⁇ 10 nm) onto sheet 200. Because the cold welding approach does not require heating, it has the advantage of reducing surface contact contamination or defect due normally attendant heating-related processes.
  • the plurality of thusly produced tape spring-type carriers 40 connected to a manifold 44 are built into neural probes 16 according to one of the exemplary structures shown in FIGs. 5 , 5A and 5B .
  • the manifolds 40 are similar to those depicted in FIG. 2 .
  • the tape spring-type carrier 40 may further extend the functionality of the system 10 by providing fluidic channels through which therapeutic drugs, drugs to inhibit biologic response to the implant, or any other suitable fluid may be transmitted. This provides for the precise delivery of specific pharmaceutical compounds to localized regions of the body, such as the nervous system, and could facilitate, for example, intraoperative mapping procedures or long-term therapeutic implant devices.
  • the fluidic channels may also provide a location through which a stiffener or stylet may be inserted to aid with implantation.
  • the carrier may further include a separate lumen through which the stiffener or stylet may be inserted.
  • a plurality of neural probes 16 constructed with a tape spring-type carrier 40 according to the present invention and deployed from an exemplary guide tube 12 increases the effective site area to allow increased charge injection while maintaining safe electrochemical and biological limits. This will enable, for example, precise current steering to selectively stimulate neural structures.
  • the thusly deployed neural probes can be used to establish one or more tunable neural interface region for the device. Multiple neural interface regions can be overlapping or non-overlapping.
  • at least two electrode sites from each probe 16 may be grouped to form a larger composite site that enables tuning the neural interface region for recording and/or stimulation. This grouping of sites can be through intrinsic connection of the site traces, or it can be through external connections for real-time tuning.
EP14189810.6A 2013-10-21 2014-10-21 Omnidirektionales, entfaltbares, neuronales Mehrkanal-Elektrodensystem Active EP2862595B1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP17175025.0A EP3254726B1 (de) 2013-10-21 2014-10-21 Omnidirektionales, entfaltbares, neuronales mehrkanal-elektrodensystem

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361893603P 2013-10-21 2013-10-21
US201361895109P 2013-10-24 2013-10-24

Related Child Applications (2)

Application Number Title Priority Date Filing Date
EP17175025.0A Division EP3254726B1 (de) 2013-10-21 2014-10-21 Omnidirektionales, entfaltbares, neuronales mehrkanal-elektrodensystem
EP17175025.0A Division-Into EP3254726B1 (de) 2013-10-21 2014-10-21 Omnidirektionales, entfaltbares, neuronales mehrkanal-elektrodensystem

Publications (2)

Publication Number Publication Date
EP2862595A1 true EP2862595A1 (de) 2015-04-22
EP2862595B1 EP2862595B1 (de) 2017-07-19

Family

ID=51752027

Family Applications (2)

Application Number Title Priority Date Filing Date
EP14189810.6A Active EP2862595B1 (de) 2013-10-21 2014-10-21 Omnidirektionales, entfaltbares, neuronales Mehrkanal-Elektrodensystem
EP17175025.0A Active EP3254726B1 (de) 2013-10-21 2014-10-21 Omnidirektionales, entfaltbares, neuronales mehrkanal-elektrodensystem

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP17175025.0A Active EP3254726B1 (de) 2013-10-21 2014-10-21 Omnidirektionales, entfaltbares, neuronales mehrkanal-elektrodensystem

Country Status (2)

Country Link
US (4) US10118030B2 (de)
EP (2) EP2862595B1 (de)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10406350B2 (en) 2008-11-12 2019-09-10 Ecole Polytechnique Federale De Lausanne Microfabricated neurostimulation device
US10441779B2 (en) 2014-08-27 2019-10-15 Aleva Neurotherapeutics Deep brain stimulation lead
US20210045690A1 (en) * 2018-03-01 2021-02-18 Universitat Basel Vizerektorat Forschung Neural probe for electrostimulation or recording and fabrication process for such a probe
US11400280B2 (en) 2016-12-22 2022-08-02 Medtronic, Inc. Deployable electrode array lead assembly for implantable electrical stimulation

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2732309C (en) 2008-07-30 2018-04-10 Ecole Polytechnique Federale De Lausanne (Epfl) Apparatus and method for optimized stimulation of a neurological target
WO2011121089A1 (en) 2010-04-01 2011-10-06 Ecole Polytechnique Federale De Lausanne (Epfl) Device for interacting with neurological tissue and methods of making and using the same
US11229789B2 (en) 2013-05-30 2022-01-25 Neurostim Oab, Inc. Neuro activator with controller
KR102363552B1 (ko) 2013-05-30 2022-02-15 그라함 에이치. 크리시 국부 신경 자극
EP2862595B1 (de) 2013-10-21 2017-07-19 NeuroNexus Technologies, Inc. Omnidirektionales, entfaltbares, neuronales Mehrkanal-Elektrodensystem
EP3476430B1 (de) 2014-05-16 2020-07-01 Aleva Neurotherapeutics SA Vorrichtung zur interaktion mit neurologischem gewebe
US11311718B2 (en) 2014-05-16 2022-04-26 Aleva Neurotherapeutics Sa Device for interacting with neurological tissue and methods of making and using the same
CA2975488C (en) * 2015-02-06 2021-09-07 Nalu Medical, Inc. Medical apparatus including an implantable system and an external system
US11077301B2 (en) 2015-02-21 2021-08-03 NeurostimOAB, Inc. Topical nerve stimulator and sensor for bladder control
US9867978B1 (en) 2016-09-16 2018-01-16 Precision Neurotechnologies Llc Conformal electrode arrays for electrophysiologic recording and neural stimulation within the cerebral ventricles
US20180117313A1 (en) 2016-10-31 2018-05-03 The Alfred E. Mann Foundation For Scientific Research Nerve cuff electrodes fabricated using over-molded lcp
EP3585475B1 (de) 2017-02-24 2024-04-03 Nalu Medical, Inc. Vorrichtung mit sequentiell implantierten stimulatoren
US11547849B2 (en) 2017-06-07 2023-01-10 Neuronexus Technologies, Inc. Systems and methods for ruggedized penetrating medical electrode arrays
CN111601636A (zh) 2017-11-07 2020-08-28 Oab神经电疗科技公司 具有自适应电路的非侵入性神经激活器
US10702692B2 (en) 2018-03-02 2020-07-07 Aleva Neurotherapeutics Neurostimulation device
CN114126704A (zh) 2019-06-26 2022-03-01 神经科学技术有限责任公司 具有自适应电路的非侵入性神经激活器
WO2021030501A1 (en) * 2019-08-12 2021-02-18 Neuroone Medical Technologies Corporation Spinal cord stimulation systems, methods, and devices
WO2021126921A1 (en) 2019-12-16 2021-06-24 Neurostim Solutions, Llc Non-invasive nerve activator with boosted charge delivery
AU2021397138A1 (en) 2020-12-10 2023-06-15 Neuronano Ab Device for insertion of microfilaments in soft tissue
AU2021455531A1 (en) 2021-07-09 2024-01-18 The Alfred E. Mann Foundation For Scientific Research Electrode leads having multi-application helical nerve cuffs and associated systems and methods
EP4306040A1 (de) 2022-07-11 2024-01-17 Atlas Neuroengineering BV Sondenvorrichtung zur schnittstellenbildung mit zellen wie z.b. neuronen und zugehörige vorrichtungen, verfahren und verwendung

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1048319A2 (de) * 1999-04-30 2000-11-02 Medtronic, Inc. System zur selektiven Aktivierung von Gehirnneuronen, Wirbelsäulenparenchyma oder periphären Nerven
US20050075681A1 (en) * 2002-02-01 2005-04-07 Ali Rezai Neural stimulation delivery device with independently moveable delivery structures
US7006859B1 (en) * 2002-07-20 2006-02-28 Flint Hills Scientific, L.L.C. Unitized electrode with three-dimensional multi-site, multi-modal capabilities for detection and control of brain state changes
US20070106143A1 (en) * 2005-11-08 2007-05-10 Flaherty J C Electrode arrays and related methods
JP2007202727A (ja) * 2006-01-31 2007-08-16 Hi-Lex Corporation 生体用電極
US7769470B1 (en) * 2002-06-24 2010-08-03 The Cleveland Clinic Foundation Neuromodulation device and method of using same
US7941202B2 (en) 2005-10-07 2011-05-10 Neuronexus Technologies Modular multichannel microelectrode array and methods of making same
CN102500055A (zh) * 2011-10-25 2012-06-20 上海交通大学 不可吸收缝合线辅助植入式柔性微电极及其制备方法
KR20120131815A (ko) * 2011-05-26 2012-12-05 알피니언메디칼시스템 주식회사 뇌신경 자극용 소형 전극 시스템의 시술 방법
US8565894B2 (en) 2007-10-17 2013-10-22 Neuronexus Technologies, Inc. Three-dimensional system of electrode leads

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5635735A (en) 1979-08-29 1981-04-08 Sumitomo Chem Co Ltd Heat resistant spring
US5803928A (en) * 1997-01-24 1998-09-08 Cardiac Pacemakers, Inc. Side access "over the wire" pacing lead
US7769472B2 (en) 2005-07-29 2010-08-03 Medtronic, Inc. Electrical stimulation lead with conformable array of electrodes
US7354033B1 (en) 2006-08-01 2008-04-08 The United States Of America As Represented By The Secretary Of The Air Force Tape-spring deployable hinge
EP2170456A4 (de) * 2007-07-11 2016-09-21 Mayo Foundation Vorhersage von krampfanfällen, mikroanfalls-vorläuferereignissen und relevante therapeutische verfahren und vorrichtungen
US8374703B2 (en) * 2009-01-26 2013-02-12 Incube Labs, Llc Method and apparatus for the detection of aberrant neural-electric activity
EP2528656B1 (de) 2010-01-27 2016-03-30 Medtronic Bakken Research Center B.V. System zur medizinischen stimulation mit einer sonde
US9008747B2 (en) 2011-03-09 2015-04-14 Neuronexus Technologies, Inc. Neural interface system with an edge array
US8954144B2 (en) 2011-06-16 2015-02-10 Neuronexus Technologies, Inc. Hybrid clustered neural interface system
EP2570153B1 (de) 2011-09-14 2017-09-13 NeuroNexus Technologies, Inc. Verfahren zur Bildung einer Elektrodenvorrichtung mit reduzierter Impedanz
EP2862595B1 (de) 2013-10-21 2017-07-19 NeuroNexus Technologies, Inc. Omnidirektionales, entfaltbares, neuronales Mehrkanal-Elektrodensystem

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1048319A2 (de) * 1999-04-30 2000-11-02 Medtronic, Inc. System zur selektiven Aktivierung von Gehirnneuronen, Wirbelsäulenparenchyma oder periphären Nerven
US20050075681A1 (en) * 2002-02-01 2005-04-07 Ali Rezai Neural stimulation delivery device with independently moveable delivery structures
US7769470B1 (en) * 2002-06-24 2010-08-03 The Cleveland Clinic Foundation Neuromodulation device and method of using same
US7006859B1 (en) * 2002-07-20 2006-02-28 Flint Hills Scientific, L.L.C. Unitized electrode with three-dimensional multi-site, multi-modal capabilities for detection and control of brain state changes
US7941202B2 (en) 2005-10-07 2011-05-10 Neuronexus Technologies Modular multichannel microelectrode array and methods of making same
US20070106143A1 (en) * 2005-11-08 2007-05-10 Flaherty J C Electrode arrays and related methods
JP2007202727A (ja) * 2006-01-31 2007-08-16 Hi-Lex Corporation 生体用電極
US8565894B2 (en) 2007-10-17 2013-10-22 Neuronexus Technologies, Inc. Three-dimensional system of electrode leads
KR20120131815A (ko) * 2011-05-26 2012-12-05 알피니언메디칼시스템 주식회사 뇌신경 자극용 소형 전극 시스템의 시술 방법
CN102500055A (zh) * 2011-10-25 2012-06-20 上海交通大学 不可吸收缝合线辅助植入式柔性微电极及其制备方法

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10406350B2 (en) 2008-11-12 2019-09-10 Ecole Polytechnique Federale De Lausanne Microfabricated neurostimulation device
US10441779B2 (en) 2014-08-27 2019-10-15 Aleva Neurotherapeutics Deep brain stimulation lead
US11400280B2 (en) 2016-12-22 2022-08-02 Medtronic, Inc. Deployable electrode array lead assembly for implantable electrical stimulation
US11904161B2 (en) 2016-12-22 2024-02-20 Medtronic, Inc. Deployable electrode array lead assembly for implantable electrical stimulation
US20210045690A1 (en) * 2018-03-01 2021-02-18 Universitat Basel Vizerektorat Forschung Neural probe for electrostimulation or recording and fabrication process for such a probe

Also Published As

Publication number Publication date
EP3254726B1 (de) 2020-07-08
US10173051B2 (en) 2019-01-08
US10118030B2 (en) 2018-11-06
US20190054293A1 (en) 2019-02-21
US20150112360A1 (en) 2015-04-23
US20190298993A1 (en) 2019-10-03
EP3254726A1 (de) 2017-12-13
US20150119673A1 (en) 2015-04-30
EP2862595B1 (de) 2017-07-19
US10842991B2 (en) 2020-11-24
US20180345010A9 (en) 2018-12-06

Similar Documents

Publication Publication Date Title
US10842991B2 (en) Neural electrode system with a carrier having a tape spring-type shape
US11324945B2 (en) Neural interface system
US8565894B2 (en) Three-dimensional system of electrode leads
US9289151B2 (en) Implantable neural interface device with a deformable carrier
US8800140B2 (en) Method of making a modular multichannel microelectrode array
US7908018B2 (en) Flexible electrode
EP2683439B1 (de) Neurales schnittstellensystem mit einem kanten-array
US20130137955A1 (en) Implantable Electrode Lead System with a Three Dimensional Arrangement and Method of Making the Same
Kipke et al. Advanced neural implants using thin-film polymers
Pothof et al. Fabrication and characterization of a high-resolution neural probe for stereoelectroencephalography and single neuron recording
CN115054265A (zh) 用于与seeg电极结合的柔性电极装置及其制造方法
CN115054257A (zh) 一种用于脑部的柔性电极及其制造方法

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20141021

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

R17P Request for examination filed (corrected)

Effective date: 20151021

RBV Designated contracting states (corrected)

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: GREATBATCH LTD.

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: NEURONEXUS TECHNOLOGIES, INC.

RIC1 Information provided on ipc code assigned before grant

Ipc: A61B 5/04 20060101ALI20161222BHEP

Ipc: A61N 1/05 20060101AFI20161222BHEP

Ipc: A61N 1/36 20060101ALI20161222BHEP

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

INTG Intention to grant announced

Effective date: 20170206

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: NEURONEXUS TECHNOLOGIES, INC.

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 909801

Country of ref document: AT

Kind code of ref document: T

Effective date: 20170815

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602014011896

Country of ref document: DE

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 4

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20170719

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 909801

Country of ref document: AT

Kind code of ref document: T

Effective date: 20170719

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171019

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171020

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171119

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171019

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602014011896

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

26N No opposition filed

Effective date: 20180420

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20171031

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20171031

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20171021

REG Reference to a national code

Ref country code: BE

Ref legal event code: MM

Effective date: 20171031

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20171031

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20171021

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 5

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20171021

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20141021

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20170719

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20221025

Year of fee payment: 9

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20221027

Year of fee payment: 9

Ref country code: DE

Payment date: 20221027

Year of fee payment: 9